We propose research aimed at clarifying the physical processes involved in transvascular fluid and solute movement in the lung and developing methods which can be used to evaluate lung microvascular function in living humans. In an unanesthetized, chronic sheep preparation, we will measure steady state hemodynamic variables and lung lymph flow and protein content under baseline conditions, during increased lung vascular pressure and during increased vascular permeability caused by Pseudomonas bacteremia. In the same experiments we will do transpulmonary indicator dilution studies across the lung with multiple indicators. We will calculate transport characteristics using several different theoretical approaches from indicator dilution data and from lymph data and compare the results. We will develop theoretical models of lung transvascular transport which are compatible with all the experimental data and determine the most precise, accurate and sensitive ways to estimate transport from indicator dilution data. In humans with several diseases in which increased lung vessel permeability is thought to occur, we will do transpulmonary indicator dilution studies identical to those in animals. Using the theoretical information gained from analyses of animal experiments, we will estimate the transport characteristics of the lung circulation in humans, attempting to clarify the role of altered vascular permeability in the diseases studied.